TY - DATA T1 - The Structure–Activity Relationship of a Tetrahydroisoquinoline Class of N‑Methyl‑d‑Aspartate Receptor Modulators that Potentiates GluN2B-Containing N‑Methyl‑d‑Aspartate Receptors PY - 2017/06/06 AU - Katie L. Strong AU - Matthew P. Epplin AU - John Bacsa AU - Christopher J. Butch AU - Pieter B. Burger AU - David S. Menaldino AU - Stephen F. Traynelis AU - Dennis C. Liotta UR - https://acs.figshare.com/articles/journal_contribution/The_Structure_Activity_Relationship_of_a_Tetrahydroisoquinoline_Class_of_i_N_i_Methyl_d_Aspartate_Receptor_Modulators_that_Potentiates_GluN2B-Containing_i_N_i_Methyl_d_Aspartate_Receptors/5144155 DO - 10.1021/acs.jmedchem.7b00239.s001 L4 - https://ndownloader.figshare.com/files/8754517 KW - GluN 2C NMDARs KW - GluN 2B subunit KW - enantiomeric pairs KW - Multiple compounds potentiate KW - CIQ KW - methoxy substituents KW - GluN 2B receptors KW - GluN 2B GluN 2B KW - isopropoxy moiety KW - isopropoxy-containing scaffold KW - GluN 2B GluN 2C KW - GluN 2C subunits KW - 2D KW - allosteric modulators KW - allosteric NMDA receptor KW - GluN 2C tetrahydroisoquinoline analogues KW - submicromolar EC 50 values KW - Tetrahydroisoquinoline Class N2 - We have identified a series of positive allosteric NMDA receptor (NMDAR) modulators derived from a known class of GluN2C/D-selective tetrahydroisoquinoline analogues that includes CIQ. The prototypical compound of this series contains a single isopropoxy moiety in place of the two methoxy substituents present in CIQ. Modifications of this isopropoxy-containing scaffold led to the identification of analogues with enhanced activity at the GluN2B subunit. We identified molecules that potentiate the response of GluN2B/GluN2C/GluN2D, GluN2B/GluN2C, and GluN2C/GluN2D-containing NMDARs to maximally effective concentrations of agonist. Multiple compounds potentiate the response of NMDARs with submicromolar EC50 values. Analysis of enantiomeric pairs revealed that the S-(−) enantiomer is active at the GluN2B, GluN2C, and/or GluN2D subunits, whereas the R-(+) enantiomer is only active at GluN2C/D subunits. These results provide a starting point for the development of selective positive allosteric modulators for GluN2B-containing receptors. ER -